Fast-flow Vascular Malformations Research Articles

Management of congenital urogenital and perineal vascular malformations: correlation of clinical findings with diagnostic imaging for treatment decision.

Analysis of clinical and diagnostic findings in rare urogenital and perineal vascular malformations only occurring in 2-3 % of vascular anomalies with regard to clinical symptoms and treatment decisions. All 25 out of 537 patients presenting with congenital urogenital and perineal vascular malformations at our institution from 2014 to 2021 were included. Vascular anomaly classification, anatomical location, clinical symptoms at presentation, diagnostic imaging, and pain intensity were retrospectively assessed from the patient record and therapy management was evaluated. In total, 25 patients (10 females (40 %), 15 males (60 %)), aged 6 to 77 years were included. Diagnoses were: 10 (40 %) venous malformations (VMs), 5 (20 %) lymphatic malformations (LMs) and 10 (40 %) arteriovenous malformations (AVMs). Malformation manifestations were: 12 (32 %) lesser pelvis, 12 (32 %) external genitalia, and 13 (34 %) perineal/gluteal region. One AVM was located in the kidney. The leading clinical symptom was pain. The mean intensity was 6.0/10 for LM, 5.7/10 for VM, and 4.5/10 for AVM. Further major symptoms included physical impairment, local swelling, and skin discoloration. Bleeding complications or sexual dysfunction were rare findings. Patients with VM reported significantly more symptoms than patients with AVM (p = 0.0129). In 13 patients (52 %) minimally invasive therapy was indicated: 10 (77 %) sclerotherapies and 3 (23 %) transcatheter embolization procedures. Complete symptomatic remission was achieved in 9 (69 %) patients, partial response in 3 (23 %) patients, and 1 patient showed no clinical response to therapy. Follow-up appointments without the need for immediate minimally invasive therapy were significantly more common in patients with AVMs than in patients with VMs (p = 0.0198). To create a higher awareness of congenital urogenital and perineal vascular malformations. Awareness of this rare condition avoids misdiagnosis. Therapy decisions should be symptom-oriented. Emergency intervention is rarely required, even in fast-flow vascular malformations. · Venous malformations cause more symptoms with higher pain intensity than arteriovenous malformations.. · Diagnosis and adequate treatment can be hampered by a lack of awareness of the clinical presentation.. · Bleeding complications are rare, even in high-flow vascular malformations.. · Pain and physical impairment are the most commonly observed symptoms in these patients..

GPRASP1 loss-of-function links to arteriovenous malformations by endothelial activating GPR4 signals.

Arteriovenous malformations (AVMs) are fast-flow vascular malformations and refer to important causes of intracerebral haemorrhage in young adults. Getting deep insight into the genetic pathogenesis of AVMs is necessary. Herein, we identified two vital missense variants of G protein-coupled receptor (GPCR) associated sorting protein 1 (GPRASP1) in AVM patients for the first time and congruously determined to be loss-of-function variants in endothelial cells. GPRASP1 loss-of-function caused endothelial dysfunction in vitro and in vivo. Endothelial Gprasp1 knockout mice suffered a high probability of cerebral haemorrhage, AVMs and exhibited vascular anomalies in multiple organs. GPR4 was identified to be an effective GPCR binding with GPRASP1 to develop endothelial disorders. GPRASP1 deletion activated GPR4/cAMP/MAPK signalling to disturb endothelial functions, thus contributing to vascular anomalies. Mechanistically, GPRASP1 promoted GPR4 degradation. GPRASP1 enabled GPR4 K63-linked ubiquitination, enhancing the binding of GPR4 and RABGEF1 to activate RAB5 for conversions from endocytic vesicles to endosomes, and subsequently increasing the interactions of GPR4 and ESCRT members to package GPR4 into multivesicular bodies or late endosomes for lysosome degradation. Notably, the GPR4 antagonist NE 52-QQ57 and JNK inhibitor SP600125 effectively rescued the vascular phenotype caused by endothelial Gprasp1 deletion. Our findings provided novel insights into the roles of GPRASP1 in AVMs and hinted at new therapeutic strategies.

Genotype–Phenotype and Genotype–Outcome Analysis of Capillary Malformation–Arteriovenous Malformation

Objective(s): Capillary malformation-arteriovenous malformation syndrome (CM-AVM) is a rare autosomal-dominant complex vascular disorder that can be associated with fast-flow vascular malformations (FFVMs). The purpose of this study is to explore the genotype–phenotype and genotype–outcome associations based on a large parallel sequencing of CM-AVM patients to improve the understanding of the development and risk factors for FFVM. Methods: A total of 117 patients with CM-AVMs were enrolled in this multicenter cohort study. All patients underwent detailed clinical phenotyping, including age, sex, capillary malformation (CM) size, with or without FFVM, and outcome (Schobinger stage). Next-generation sequencing was performed with peripheral blood and tissue samples. Genotype–phenotype, genotype–outcome, and phenotype–outcome analyses were performed. Results: Germline or mosaic RASA1 variants were the most common cause of CM-AVM, found in 61.5%, with EPHB4 variants in 32.5%. A total of 76.9% of patients had a dominant CM lesion larger than 5 cm. No obvious correlations between genotypes and phenotypes, including sex, age, location, and size of CMs, were found in this cohort. Comparing the patients with FFVMs with those without FFVMs, we found significant differences in age and the size of dominant CM lesions but not in genotype, sex, or location. Conclusion: CM-AVMs can be categorized as complex vascular malformations caused by different gene alterations in the RAS/RAF/MEK pathway. No obvious correlations between genotypes and phenotypes were identified. Critically, the occurrence and progression of FFVM is strongly determined by phenotypes, including age and the size of the dominant CM, rather than genotypes.

Capillary Malformation-Arteriovenous Malformation Type 2, A Report of 6 Cases and Main Differential Diagnosis

Objectives: Capillary malformation-arteriovenous malformation (CM-AVM) is a rare disorder characterized by multifocal CMs associated with AVMs. While the phenotype of CMAVM1 has been well established in the literature, there are limited published reports documenting the clinical features of CMAVM2. Our aim is to highlight this phenotype, and the distinctive features of CMAVM2 compared with CMAVM1 and hereditary hemorrhagic telangiectasia, as prompt recognition is crucial to screen for fast-flow vascular malformations, which, if left untreated, can sometimes be life-threatening. Methods: This is a retrospective review of cases seen at multiple tertiary care centers in the United States and Argentina. Results and Conclusions: We report 6 pediatric patients with CMAVM2 presenting with diffuse multifocal cutaneous CMs, telangiectases favoring the lips, perioral area and upper trunk, and Bier spots. Three patients had epistaxis. One patient had an extracranial AVM and 1 patient had Parkes Weber syndrome. EPHB4 pathogenic variants were identified in all patients. CMAVM2 remains an underrecognized condition. Genetic testing and imaging studies are recommended to guide management.

Dermatoscopic features differentiating among port wine stain, arteriovenous malformation, and capillary malformation-arteriovenous malformation syndrome: to detect potential fast-flow vascular malformations at an early stage

To the Editor: Arteriovenous malformations (AVMs), capillary malformation-arteriovenous malformations (CM-AVMs), and port wine stains (PWSs) are different vascular anomalies that can present with similar morphology but differ in genetics, pathogenesis, progression, treatment, and prognosis.1-3 Early AVMs and CM-AVMs may mimic PWS clinically, leading to misdiagnosis and inappropriate management. In this study, we sought to determine the dermatoscopic features of AVMs and CM-AVMs, compare them with those of PWSs (controls) in a blinded manner, and detect potential fast-flow vascular malformations (FFVMs) at an early stage.

Central nervous system screening in capillary malformation-arteriovenous malformation syndrome: An observational study

To the Editor: Capillary malformation-arteriovenous malformation (CM-AVM) is an autosomal dominant disorder characterized by small, multifocal capillary malformations (CMs), sometimes skin telangiectasias, and increased risk of fast-flow vascular malformations, mostly arteriovenous malformations (AVMs) located in the central nervous system (CNS) and soft tissues.1,2 Pathogenic variants of RASA1 (CM-AVM type 1 [CM-AVM1]) and EPHB4 [CM-AVM2] are identified in about 50% and 25% of patients, respectively.

Vascular Birthmarks as a Clue for Complex and Syndromic Vascular Anomalies.

Vascular birthmarks are common in neonates (prevalence: 20–30%) and mostly incidental findings sometimes with spontaneous regression (salmon patch and nevus simplex). Capillary malformations are found in about 1% and infantile hemangiomas are found in 4% of mature newborns. Vascular malformations are classified according to their most prominent vessel type. The term “capillary malformation” (port wine stain) includes a wide range of vascular lesions with different characteristics; they may be isolated or part of specific syndromic conditions. Part of the infantile hemangiomas and of the vascular malformations may require treatment for functional or cosmetic reasons, and in rare cases, investigations are also necessary as they represent a clue for the diagnosis of complex vascular malformation or tumors associated with extracutaneous abnormalities. Complex vascular malformations are mostly mosaicism due to early somatic mutations. Genetic advances have led to identify the main pathogenic pathways involved in this disease group. Diffuse capillary malformation with overgrowth, Klippel–Trenaunay syndrome, CLAPO syndrome, CLOVES syndrome, and megalencephaly-capillary malformation belong to the PIK3CA-related overgrowth. Capillary malformation–arteriovenous malformation underlies a fast-flow vascular malformation, sometimes manifesting as Parkes–Weber syndrome. Recognition of these different types of capillary vascular stains is sometimes difficult; however, associated findings may orient the clinicians while genetic testing may confirm the diagnosis. Lymphatic malformation frequently manifests as large masses that compress and/or infiltrate the surrounding tissues, representing a neonatal emergency when airways are involved. Infantile hemangiomas may cause functional and/or permanent esthetical damage, depending on their localization (such as periorbital area, lip, nose); large (more than 5 cm) infantile hemangiomas with a segmental distribution can be associated with obstruction or malformations of the underneath organs with complications: PHACE syndrome, LUMBAR/SACRAL syndrome, and beard infantile hemangioma. In our review, we discuss controversies regarding the international classification and emerging concepts in the field of vascular anomalies. Finally, we discuss potential developments of new, non-invasive diagnostic techniques and repurposing of target therapies from oncology. Complex and/or life-threatening vascular tumors and malformations are extremely rare events and they represent a considerable therapeutic challenge. Early recognition of clinical signs suggestive for a specific disease may improve therapeutic outcomes and avoid severe complications.

Capillary malformation-arteriovenous malformation syndrome: a multicentre study.

Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is a rare syndrome with characteristic skin lesions that are associated with fast-flow vascular malformations (FFVMs) in one-third of patients. Few case series have been described, and none in Spain. To identify the prevalence of dermatological parameters, FFVMs and associated features in a large series of patients with CM-AVM. We conducted an observational study of patients with CM-AVM syndrome diagnosed in 15 Spanish hospitals over 3years. The main clinical, radiological, genetic findings and associated diseases were analysed. In total, 64 patients were assessed. In 26.5% of cases, the diagnosis was incidental. In 75% of patients, there was one significantly larger macule, which we termed the 'herald patch'. FFVMs were detected in 34% of the patients, with 30% located on the skin, 7.8% in the brain and in 1.5% in the spine. There was a positive family history in 65% of the 64 patients. Genetic analysis was performed for RASA1 mutations in 57 patients, of whom 42 (73%) had a positive result. All 4 patients tested for EPHB4 mutations had a positive result. No tumour lesions were detected in the series, except for five infantile haemangiomas. Our data on clinical lesions, associated FFVM, family history and genetics are similar to those previously published in the literature. An extensive data analysis failed to demonstrate any statistically significant association between the presence of an FFVM and any clinical, familial or genetic parameter that could predict its onset, although a link between the presence of a herald patch on the midline face and the presence of a brain FFVM was observed. We did not detect any genotype-phenotype correlation.

RASA1 mosaic mutations in patients with capillary malformation-arteriovenous malformation

BackgroundCapillary malformation-arteriovenous malformation is an autosomal dominant disorder, characterised by capillary malformations and increased risk of fast-flow vascular malformations, caused by loss-of-function mutations in the RASA1 or EPHB4 genes. Around...

Vascular Anomalies (Part II): Interventional Therapy of Peripheral Vascular Malformations.

The International Society for the Study of Vascular Anomalies (ISSVA) categorizes vascular anomalies into vascular tumors and vascular malformations. Vascular malformations are further divided into slow-flow (venous, lymphatic, and capillary malformation) and fast-flow malformations (arteriovenous malformation and arteriovenous fistula). This interdisciplinary classification has therapeutic implications. The objective of this article is to provide concise information about the current terminology and treatment strategies of peripheral vascular malformations, based on the currently available literature, with a focus on interventional therapy of venous malformations (VM), lymphatic malformations (LM), arteriovenous malformations (AVM) and arteriovenous fistulae (AVF). Accurate classification is crucial for appropriate therapy of peripheral vascular malformations. Modern imaging technologies and refined interventional treatment strategies are now central parts in the multidisciplinary management of these patients. Slow-flow and fast-flow vascular malformations can be treated successfully by percutaneous sclerotherapy and endovascular embolotherapy as first-line interventions. · The ISSVA classification is essential for the correct diagnosis of vascular malformations. · The Schobinger classification as well as the Cho classification should be used for description of arteriovenous malformations (AVM). · Sclerotherapy and embolotherapy are the primary treatments of choice for vascular malformations. · Müller-Wille R, Wildgruber M, Sadick M et al. Vascular Anomalies (Part II): Interventional Therapy of Peripheral Vascular Malformations. Fortschr Röntgenstr 2018; DOI: 10.1055/s-0044-101266.

Ileal angiodysplasia causing chronic, occult gastrointestinal bleeding in a 14-year-old boy

Abstract A 14-year old boy with anemia due to chronic gastrointestinal bleeding required recurrent transfusion. An extensive non-invasive evaluation that included detection of fresh blood in the small bowel followed by laparotomy with on-table pan-endoscopy (including enteroscopy) was unsuccessful in identifying a bleeding source. After repeat capsule endoscopy at our center confirmed bleeding in the distal small bowel, CT angiography identified a 6-mm focal area of enhancement in the ileum communicating with a distal branch of the superior mesenteric artery. Direct visceral angiography with super-selective arteriography identified a fast-flow vascular malformation supplied by terminal branches of the ileal artery. Diagnostic laparoscopy revealed intra-abdominal adhesions and no clear vascular malformation. Initial careful visual and manual examination of the bowel after conversion to laparotomy failed to identify the lesion. On-table retrograde enteroscopy demonstrated a small, pulsatile lesion without ulceration or adherent clot in the mucosa of the proximal ileum. With endoscopic transillumination, a cluster of serpiginous vessels could be seen within the wall of the small bowel. The lesion was resected and pathology was consistent with angiodysplasia. Angiodysplasia is a rare cause of occult, chronic gastrointestinal bleeding in children. A multidisciplinary approach optimizes the likelihood of therapeutic success.

Atypical MRI features in soft-tissue arteriovenous malformation: a novel imaging appearance with radiologic-pathologic correlation.

The absence of a discrete mass, surrounding signal abnormality and solid enhancement are imaging features that have traditionally been used to differentiate soft-tissue arteriovenous malformations from vascular tumors on MRI. We have observed that these findings are not uncommon in arteriovenous malformations, which may lead to misdiagnosis or inappropriate treatment. To estimate the frequency of atypical MRI features in soft-tissue arteriovenous malformations and assess their relationship to lesion size, location, tissue type involved and vascular architecture. Medical records, MRI and histopathology were reviewed in consecutive patients with soft-tissue arteriovenous malformations in a multidisciplinary vascular anomalies clinic. Arteriovenous malformations were divided into those with and without atypical MRI findings (perilesional T2 signal abnormality, enhancement and/or a soft-tissue mass). Lesion location, size, tissue involved and vascular architecture were also compared between groups. Tissue stains were reviewed in available biopsy or resection specimens to assess relationships between MRI findings and histopathology. Thirty patients with treatment-naïve arteriovenous malformations were included. Fifteen lesions demonstrated atypical MRI. There was no difference in age, gender, lesion size or involved body part between the groups. However, more than half of the atypical lesions demonstrated multicompartmental involvement, and tiny intralesional flow voids were more common in atypical arteriovenous malformations. Histopathology also differed in atypical cases, showing densely packed endothelial cells with connective tissue architectural distortion and edema. Arteriovenous malformations may exhibit features of a vascular tumor on MRI, particularly when multicompartmental and/or containing tiny internal vessels. These features are important to consider in suspected fast-flow vascular malformations and may have implications with respect to their treatment.

Arteriovenous malformations

Arteriovenous malformations (AVMs) are fast-flow vascular malformations composed of a complex vessel network directly connecting feeding arteries to draining veins. The intervening normal capillary network is absent. Proper diagnosis and treatment of AVMs is challenging and in need of an interdisciplinary team of experienced physicians. Careful analysis of the clinical features and evaluation of therapeutic options represent the basis for successful management of AVMs. This article will focus on the clinical and radiological findings and in particular on interdisciplinary management strategies of AVMs including minimally invasive endovascular and surgical treatment.

Capillary malformation–arteriovenous malformation: a clinical review of 45 patients

Capillary malformation-arteriovenous malformation (CM-AVM) is a recently described autosomal dominant disorder that results from mutations in RASA1. It has been initially described as multiple CMs affecting several members of the same family, associated with fast-flow malformations in at least one family member. To report and analyze clinical data on 45 patients with CM-AVM assessed at the Department of Pediatric Dermatology, Ramos Mejía Hospital (Buenos Aires, Argentina). Retrospective clinical review of all the patients clinically diagnosed as having CM-AVM over a period of eightyears. Forty-five patients were recorded (24 females and 21 males). The age ranged from onemonth to 44years. In 36 patients, the stains were congenital; progressive acquired lesions were observed in 39. Family history was positive in 32 subjects. Well defined, round to oval, pink-purple or reddish-brown macules were found in all the patients; pinpoint red lesions with a pale halo were found in nine cases. The macules were warmer than normal skin in 15 cases and surrounded by a white halo in 26 cases. Three subjects presented associated overgrowth, lymphatic malformation was present in one case, retinal vascular lesion in one patient, and isolated port wine stain in two cases. Three patients also had infantile hemangioma. We had no cases of fast-flow vascular malformation or combined vascular syndromes. CM-AVM is a heterogeneous disorder with phenotypic variability, from fast-flow malformation, limb enlargement, or Parkes Weber syndrome to multiple CMs without internal involvement.

In vivo synergetic effect of in situ sclerotherapy and transient embolotherapy designed for fast-flow vascular malformation treatments with the aid of injectable hydrogel.

Fast-flow vascular malformations are very difficult to treat by the currently available drug delivery systems due to the particular obstacles associated with rapid blood flow. The goal of the present study is to address such a challenge through a novel chemotherapy approach with the aid of injectable hydrogel. Specifically, a pingyangmycin (PYM)/PECE hydrogel is purposely designed with a programmed synergetic therapy mechanism involving the transient embolotherapy of hydrogel and in situ chemotherapy induced by the locally released drug in a sustained manner. This formulation remained mobile at room temperature whereas rapidly undergoing in vivo sol-gel transition upon injection into the body. The sustained release characteristic of PYM/PECE formulation was revealed both in vitro and in vivo. All the pharmacokinetic characteristics were highly improved including the Tmax, Cmax, t1/2β and AUC(0-t). The exceptional efficacy of PYM/PECE formulation was validated by rapid vascular occlusion in rabbit's fast-flow central auricular arteries whereas respective PYM and PECE treatment failed. The most remarkable features included the precise control over the occlusion site and the irreversible formation of vessel-isolated cell-rich lumps that was believed to benefit the occlusion formation. Intravascular PYM/PECE administration induced neither toxic responses nor histopathological changes in rabbits' major organs. The hydrogel matrix could be completely absorbed in vivo. The present study highlighted the great promise of our design as a safe and extremely effective modality in the treatment of fast-flow vascular malformations.

Safety and Clinical Efficacy of Onyx for Embolization of Extracranial Head and Neck Vascular Anomalies: Fig 1.

Onyx was developed for embolization of central nervous system AVMs but is increasingly used extracranially because of its unique physical properties. We review our experience and results with the use of Onyx for the treatment of fast-flow extracranial vascular lesions. We retrospectively analyzed clinical and imaging records of 22 patients who underwent 71 extracranial embolizations from March 2007 through January 2010. The diagnoses were the following: cervicofacial AVM (n = 18), traumatic fistula (n = 3), and vessel laceration (n = 1). In 62 of 71 procedures (87%), Onyx was the sole embolic agent; it was delivered transarterially in 67/71 and percutaneously in 4/71 procedures. Clinical goals included amelioration of pain and control of bleeding. The clinical efficacy of embolization was judged by symptom control, and adverse events were assessed by clinical examination and history, both postembolization and 4 weeks postprocedure. Cessation of acute bleeding was achieved in 13/14 cases, with 1 case of immediate recurrent massive epistaxis prompting reintubation and further embolization. Control of subacute bleeding episodes and pain was achieved for all patients. Following staged embolization, 7 patients underwent surgical resection without significant blood loss. Surgeons reported high satisfaction with the intraoperative handling properties of Onyx. Transient swelling, local tenderness, or numbness was encountered after 7 procedures. There were no stuck catheters, vessel dissections, or vessel ruptures and no skin discoloration. Staged Onyx embolization was clinically efficacious in managing extracranial fast-flow vascular malformations and lesions, with low associated morbidity.

Head and neck vascular anomalies in children

Vascular lesions are the most common congenital and neonatal abnormalities. The aim of this work is to point out differences between various vascular anomalies, in order to define accurate diagnosis, and to present different therapeutic options now used for the treatment of the vascular lesions in children. According to biological classification described by the work of Mulliken and Glowacki there are two major types of vascular abnormality: haemangioma and vascular malformation. Haemangioma is a distinct biologic tumour entity characterised by rapid endothelial proliferation shortly after birth. The lesion is absent at birth and growth in early infancy, followed by a spontaneous resolution in childhood. Vascular malformations are structural anomalies that have a normal growth rate and endothelial turnover. According to the morphology of the vessels and the flow rate we distinguish: slow-flow and fast-flow vascular malformation. The authors document their personal experience in diagnosis, clinical evaluation, treatment and follow-up of the vascular lesions.

Vascular anomalies and the growth of limbs: a review

Growth of the limb in a child can be impaired, with the coexistence of a vascular malformation. In these vascular bone syndromes, altered growth is manifest as overgrowth or hypotrophy. The vascular malformation is usually complex and gets progressively worse with time. The two types of vascular anomalies in limbs, fast-flow and slow-flow, can be associated with limb length discrepancies. The fast-flow vascular malformations together with arteriovenous fistulae are part of Parkes Weber syndrome, characterized by congenital red cutaneous staining, hypertrophy in girth and increasing of limb length, lymphedema, increasing skin alterations due to a distal vascular steal, and pain, all of which develop during childhood. Treatment is generally conservative. An affected lower extremity can be complicated by pelvic tilting and scoliosis because leg length discrepancy may reach 10 cm. To avoid such a course, stapling epiphysiodesis of the knee cartilages is often performed, but this orthopedic procedure may augment the worsening of the arterial venous malformation in the limb. Therefore, less aggressive orthopedic management is preferable. Slow-flow vascular anomalies associated with limb growth alteration include (1) a diffuse capillary malformation (port-wine stain) with congenital hypertrophy of the involved extremity which is non-progressive; (2) purely venous malformations invading skin, muscles and joints, with pain, functional impairment, a chronic localized intravascular coagulopathy requiring distinctive management, and usually a slight undergrowth of the affected extremity and progressing amyotrophy; (3) the triad of a port-wine stain, anomalous veins and overgrowth of the limb, often known as Klippel-Trenaunay syndrome, which requires orthopedic management to decide the optimal timing for epiphysiodesis (i.e. when leg length discrepancy is >2.5 cm). Varicose veins are sometimes surgically removed after ultrasonographic and Doppler evaluation has confirmed a normal deep venous system. Capillary malformations can be effectively treated with pulsed dye laser, but results are usually poor in distal extremities.